update and current status on prospect ii/prospect...
TRANSCRIPT
Update and current status on
PROSPECT II/PROSPECT ABSORB
Optics in Cardiology
Zurich 2018
Prof David ErlingeDept of Cardiology
Lund University
Lund, Sweden
Non-Flow Limiting Vulnerable Plaque
• A plaque that is non-flow limiting, but will cause a
coronary event.
• FFR/iFR can by definition not detect Non-flow
limiting plaques.
• We need other methods to detect these plaques
Lipid in PlaqueThin Cap Fibroatheroma
with rupture (70%)
Lipid core in all
Erosion (no obvious rupture (30%)
Lipid pool in both (about 50% have lipid pool (M Joner
personal communication)
Calcified nodule (2-5%). No lipid.
Approximately 85% of plaques causing
sudden death have lipid core or lipid pool
Falk et al., EHJ 2013
Lund-Stockholm outcome study
Improvements
• Both 20 and 50 MHz ultrasound giving
“OCT-like” resolution combined with
depth
• 4 x faster pullback
• Thin cap detection with collagen
algorithm
NIRS technology: Intravascular Diffuse Reflectance
5
Vessel Wall
SpecularReflections
Diffuse Reflectance
detected
NIRS Light
Uncollected light
• The returned near infrared light along with knowledge of the delivered light allow computation of absorption spectra
• Absorption spectra can be used to identify molecules
Absorbance Spectra
NIRS generated Chemogram
maxLCBI4mm: 0-1000
Erlinge, (review) J Internal Medicine 2015
NIRS-IVUS in pathology specimens
(NIRS)-IVUS detects plaque volume• Intravascular ultrasound
(IVUS) can see External
Elastic Lamina (EEL) and
Lumen.
• EELarea-Lumenarea/EELarea=
Plaque Burden PB/Percent
Atheroma Volume (PAV)
Plaque
burden/
volumeLumen
Lumen
EEL
McPherson JA et al. JACC Img 2012;5:S76–85; Stone, GW et al., NEJM, 2011.
The prospective importance of plaque burden has been confirmed in the
PREDICTION and VIVA trials: Stone,P Circ 2012, Calvert JACC CVI 2011
Me
dia
n 3
.4 y
r M
AC
E r
ate
pe
r le
sio
n (
%)
0,0%0,6% 0,5%
2,5%
9,5%
0%
2%
4%
6%
8%
10%
12%
<40% 40% - 50%(n=904)
50% - 60%(n=1,239)
60% - 70%(n=798)
≥70% (n=298)
Plaque burden
thousands
PROSPECT: Correlates of Non-culprit Lesion
Related Events: Impact of plaque burden
31% of pts having at least one non-culprit
lesions with PB≥70%
But only 28 of these 298 >70% plaques
caused a coronary event
NNT = 11
Plaque
burden
>70%
Lumen
Lipid rich plaques defined by NIRS cause STEMI
Typical circular lipid-rich plaque with MaxLCBI4mm of 920 in LAD in a
patient with an inferior STEMI. Erlinge, (review) J Internal Medicine 2015
Core lab confirmation of a NIRS
treshold for STEMI plaques
Confirmation that MaxLCBI4mm >400 is detected in the majority of STEMI culprit
plaques
Madder…Erlinge, ATVB 2016
A cut-off of maxLCBI >400 had high sensitivity and specificity to detect a culprit
NSTEMI plaque
NSTEMI and Unstable angina culprit plaques have
more lipid as detected with NIRS
Madder…Erlinge, Catheterization Cardiovascular Interventions, 2014
NIRS and Plaque Burden
Khan… Madder, abstract TCT 2015
Rarity of Non-culprit PB70 Lesions with Concurrent Large Lipid BurdenWhereas PB70 lesions accounted for 12.0% of all non-culprit plaques, PB70 lesions with a concurrent
maxLCBI4mm ≥400 are rare, accounting for only 2.1% of all non-culprit lesions.
NIRS added to Plaque Burden
Khan… Madder, abstract TCT 2015
Two Lesions Having a Large Plaque BurdenThis figure highlights the ability of combined NIRS-IVUS imaging to
differentiate lesions having a large PB into those with (left) and without (right)
substantial lipid content.
Post-thrombectomy
LCBI: 604
LCBI: 466
Thrombus and Lipid-rich Aspirate
Reduced lipidcore in NIRS.
Pre-thrombectomy
In vivo histological validation of NIRS detecting lipid
rich plaque
Erlinge et al, EHJ CV imaging 2014
Pre-thrombectomy Post-Thrombectomy0
200
400
600
800
LCBI
p = 0.0001
Pre-thrombectomy Post-Thrombectomy0
200
400
600
800
1000
maxLCBI 4mm
p = 0.001
Thrombectomy is Coronary Liposuction
Erlinge et al, EHJ CV imaging 2014
NIRS in non-culprit plaquespredicts clinical
outcomes• Pooled Atheroremo-NIRS and
IBIS-3 – Serruys
• Large single-center registry with extended FU – Madder
• ORACLE-NIRS – Brilakis
• Sweden-NIRS - Erlinge
Schuurman et al., EHJ 2017
Danek et al., CV Revasc Med 2017
Karlsson…Erlinge, submitted
• LCBI and maxLCBI in non-culprit segments strongly predicts MACE
Madder et al, EHJ CVI 2016
Prospective Identification by NIRS of a Lipid-
Rich Plaque that Caused a Myocardial Infarction
Site of Index
MI –was stented
Possible Vulnerable
Plaque in LAD
4 Months
New MI
New culprit
lesion
at lipid-rich site.
• High lipid in D1 (first culprit) and in prox LAD.
• maxLCBI4mm: 722 in D1, 573 in LAD
NIRS: Lipid rich, collagen low plaque predicted NSTEMI and
ruptured plaque
Lipid detection algorithm (yellow)
Collagen detection algorithm (red)
(only measured in lipidrich areas)
LAD ruptured plaque 4 months later
White areas indicating thin cap (low collagen) in LAD plaque
PROSPECT II Study900 pts with ACS at 16 hospitals
NSTEMI or STEMI >12h
IVUS + NIRS (blinded) pre-PCI in culprit vessel(s)
Successful PCI of all intended lesions (by angio ± FFR/iFR)
Formally enrolled
IVUS + NIRS (blinded) (prox 6-10 cm of each coronary artery)
3-vessel imaging post PCI
Angiography to core lab: Adjudication to non-culprit or culprit lesion.
IVUS + NIRS if possible
Coronary Event
PI: David Erlinge
Chairman: Gregg Stone
Enrollment complete dec 2017: 902 patients
• Primary endpoint: Patient level non-culprit lesion-related major adverse
cardiac events (NC-MACE) through 2 years: cardiac death, MI, unstable
angina/progressive angina requiring repeat hospitalization or symptom-
driven revascularization by CABG or PCI, adjudicated to an originally
untreated non-culprit lesion.
PROSPECT II (Natural History Study):
PRIMARY ENDPOINT
PROSPECT II Study
PROSPECT ABSORB RCT
900 pts with ACS after successful PCI3 vessel IVUS + NIRS (blinded)
≥1 IVUS non-flow limiting lesion with ≥70% plaque burden?
Routine angio/3V IVUS-NIRS FU at 2 years
Yes(N=182)
No(n=720)
ABSORB BVS
+ GDMT (N~100)
GDMT(N~100)
R
1:1
Clinical FU for ≥2 years (up to 15 years in registers)
PROSPECT ABSORB, The ABSORB BVS
Neo-media vascular
smooth muscle cells
Cap sealing
PROSPECT ABSORB
PRIMARY ENDPOINT
• The minimal luminal area (MLA) at the randomized
non-culprit lesion site in patients treated with the
ABSORB BVS + GDMT compared to GDMT only
measured at 25 months (superiority)
• Death, TV-MI, TLR (noninferiority, not powered)
MLAMLA
2 years
”Plaque Sealing”
Follow up in P2/PA• 95% 2y follow up in PROSPECT2
• 87% angiographic follow up at 25 month in PROSPECT ABSORB
ABSORB II: 3 year data
• Depressing results
Serruys et al, Lancet 2016
SAFETY PROSPECT ABSORB
• In PROSPECT ABSORB we have not seen any definite stent thrombosis
• Some minor complications: Occluded side branch, distal dissection, one restenosis upon reexamination.
• Most PROSPECT ABSORB patients in Lund look great at reexamination
• DSMB (Serruys, Koenig, Tijssen and Wykrzykowska) recommended the study to continue at the last DSMB meeting. However, they recommended PSP technique and DAPT for 2 years.
• 25 months follow up completed dec 2019